Search Results (1,508)

The galactose/N-acetyl-D-galactosamine (Gal/GalNAc)-inhibitable lectin of Entamoeba histolytica plays essential roles in host cell adhesion and cytotoxicity. The intermediate subunit lectin-1 (Igl1) contributes to these functions, but its molecular state under different environmental conditions remains unclear. In this study, we found that Igl1 is present as multiple fragments in the culture supernatant of trophozoites, whereas a single major species corresponding to intact Igl1 was detected in cell lysates. Notably, the molecular sizes of both intact Igl1 and its extracellular fragments differed depending on culture conditions, with larger apparent sizes observed under co-culture with Caco-2 cells. These differences were not explained by changes in transcript levels, protein folding, or N-terminal truncation. Fragmentation of Igl1 was suppressed by a cysteine protease inhibitor, indicating extracellular generation. These findings demonstrate that host-cell-associated conditions alter the molecular size of Igl1 and that extracellular protease-dependent processing generates multiple Igl1 fragments, providing new insights into the regulation of this key virulence factor. The presence of extracellular fragments further suggests a potential contribution to host tissue damage during amoebiasis. Full article

Pseudomonas aeruginosa, an opportunistic pathogen, is a major threat to hospital infection control and global public health due to its strong environmental adaptability, complex virulence systems, efficient biofilm formation capability, and widespread multidrug resistance. Traditional single-target antibiotics are often inadequate for clinical treatment. The research into Plant-Derived Bioactive Compounds for combating P. aeruginosa infections is reviewed, highlighting their advantages (many of which are extensively studied in Traditional Chinese Medicine) over conventional antibiotics. The antimicrobial mechanisms of these compounds include the inhibition of bacterial quorum sensing (QS) systems to suppress virulence factor expression rather than direct anti-bactericidal effects, delaying the development of resistance. The abundant natural medicinal plants and their diverse chemical structures provide ample material for active compound screening to identify unique chemical compositions with specific binding to pathogen targets. Plant-Derived Bioactive Compounds exhibit excellent safety profiles, targeting bacterial-specific pathways or host immune regulation, resulting in minimal off-target toxicity. Plant-Derived Bioactive Compounds exert anti-P. aeruginosa effects via inhibition of QS systems to reduce pathogenicity by disrupting intercellular signaling, suppressing biofilm formation/maturity to overcome biofilm-associated resistance, directly interacting with bacterial structure. Plant-Derived Bioactive Compounds are promising treatments for drug-resistant P. aeruginosa infections, providing lead compounds for novel anti-infective drug development. Full article

Sclerotinia sclerotiorum is a formidable soilborne fungus that wreaks havoc on numerous crops globally. While the role of ADP-ribosylation factor-like 1 (Arl1) small GTPases in vesicular trafficking and fungal development is well-documented, their specific impact on S. sclerotiorum remains unclear. Through reverse genetic techniques, we identified and characterized SsArl1, a typical Arl small GTPase conserved across fungi. Deleting SsArl1 hampers the hyphal growth of S. sclerotiorum, but leads to higher oxalic acid buildup and boosts cellulase activity. This speeds up the infection of host plants, yet increases their sensitivity to certain environmental stresses, particularly ionic and cell wall-related stress. Our results reveal that SsArl1 acts as a negative regulator of oxalic acid accumulation and virulence, while playing a positive role in enhancing resistance to environmental stresses in S. sclerotiorum. Full article

Lactobacilli species have emerged as a focal point in food microbiology due to their core probiotic properties, including the regulation of intestinal homeostasis and the enhancement of immunity. This study focuses on Lacticaseibacillus rhamnosus MG0718 (hereinafter referred to as MG0718), employing a combined approach of phenotypic evaluation and whole-genome sequencing to assess its probiotic potential and analyze the correlation between its phenotype and genotype. In vitro experiments demonstrated that MG0718 possesses broad-spectrum antibacterial activity against pathogenic bacteria. In vitro experiments showed that MG0718 had broad-spectrum antibacterial activity against pathogenic bacteria such as Escherichia coli (E. coli), with an inhibition zone diameter of up to 13.67 ± 1.56 mm. It survived pH 2.5 for 6 h with only a 1.72 log10 reduction, and showed 0.78 and 1.11 log10 CFU/mL reductions in artificial gastric and intestinal fluids after 2 h. DPPH scavenging was 56.7% and total reducing power was 91.1%. In vivo, 7-day preventive administration maintained 100% survival against S. Typhimurium infection and alleviated weight loss. Bacterial loads in spleen, liver, and cecum dropped from 4.5, 4.5, and 4.2 to 3.6, 1.8, and 2.5 lg CFU/g, respectively. Whole-genome sequencing analysis indicated that the complete genome of MG0718 is 2,574,565 bp in length, containing 2813 CDS. Among these genomic components, 203 stress-related protein genes elucidate its superior environmental tolerance; one bacteriocin gene cluster, one EPS gene cluster and two secondary metabolite gene clusters provide the genetic basis for its antibacterial activity. Notably, no virulence factors were detected, ensuring the safety of the strain for application. In summary, the functional phenotypes of MG0718 are highly consistent with its genetic characteristics, identifying it as a probiotic candidate of significant developmental value. Future research should focus on clinical trials to further verify its practical benefits for human intestinal health and immunomodulation, thereby providing a robust scientific basis for its application in functional foods. Full article

Vibrio splendidus is an important opportunistic pathogen that causes diseases in aquatic animals, and its persisters increase the difficulty of aquaculture disease control. The stringent response is a central pathway in bacteria for coping with environmental stress, and the signaling molecule (p)ppGpp, synthesized under the regulation of RelA/SpoT homologs, is closely associated with persister formation and virulence modulation. However, the regulatory mechanisms linking the stringent response to persister formation and virulence in V. splendidus remain unclear. In this study, the core gene deletion strains ΔrelA and ΔrelAΔspoT were constructed via homologous recombination. Combined with D₂O single-cell Raman spectroscopy, transcriptomics, and phenotypic assays, we systematically characterized the biological effects of stringent response inactivation. The results showed that the loss of relA and spoT significantly reduced persister formation and key virulence traits while enhancing biofilm formation. Single-cell Raman spectroscopy analysis indicated that persisters remained metabolically active, accompanied by changes in different cellular components. Transcriptome analysis revealed that the absence of stringent response affected multiple pathways, including ribosomal function, energy metabolism, two-component systems, and quorum sensing. Additionally, the sigma factor RpoS may potentially exert a compensatory function in ΔrelAΔspoT strain, but this requires further validation. In conclusion, the stringent response positively regulates persister formation and virulence in V. splendidus, despite the existence of complex regulatory mechanisms. This study provides a theoretical basis for the development of anti-infective strategies targeting stringent response in aquatic pathogens. Full article

The mitochondrial membrane protein UPS1, a conserved intermembrane space protein in Saccharomyces cerevisiae, possesses phosphatidic acid transfer activity and plays a positive regulatory role in processes such as cardiolipin metabolism and transport. The role of UPS1 protein in pathogenic fungi such as Candida albicans has not been explored, especially in relation to its influence on virulence factors like hyphal growth and biofilm formation, which are crucial for the pathogenicity of C. albicans. The research investigated the function of the UPS1 protein in C. albicans by using gene knockout techniques, analyzing mitochondrial function, and conducting tests for hyphal and biofilm development. The results revealed that deletion of the UPS1 gene leads to altered mitochondrial morphology, increased reactive oxygen species levels, and reduced intracellular ATP content, thereby causing severe growth defects in C. albicans. In addition, transcriptomic analysis indicated that loss of UPS1 significantly represses the expression of genes associated with hyphal growth and biofilm formation. Functional assays further confirmed that UPS1 deficiency markedly impairs cell adhesion capability, hyphal development, and biofilm formation of C. albicans. Notably, deletion of the UPS1 protein markedly reduces the susceptibility of C. albicans to membrane-targeted antifungal drugs. Finally, infection models using Galleria mellonella larvae and a murine vulvovaginal candidiasis model verified that UPS1 gene knockout attenuates the pathogenicity of C. albicans. In summary, our findings demonstrate that UPS1 protein modulates the pathogenicity of C. albicans by regulating mitochondrial function, hyphal growth, and biofilm formation. Full article

Prophages are bacteriophage genomes that are part of bacterial chromosomes. They are not just dormant passengers; they actively shape pathogen biology. For example, in skin-infecting pathogens such as Staphylococcus aureus, Streptococcus pyogenes, and Pseudomonas aeruginosa, prophages carry important virulence factors, cytotoxins, superantigens, immune evasion clusters, and epigenetic regulators that directly affect the course of skin and soft tissue infections. This same prophage biology provides a therapeutic strategy: prophage-derived molecules, including endolysins, holins, spanins, and polysaccharide depolymerases, demonstrate potent antimicrobial and antibiofilm activity against drug-resistant skin pathogens, with several candidates now in clinical development. Engineered chimeric lysins, CRISPR-encoded prophage delivery systems, and the systematic mining of the skin microbiome phageome collectively enhance the translational potential of this biology. This review integrates mechanistic insights into prophage-mediated virulence. It assesses the translational landscape of prophage-derived therapeutics, delineating the conceptual and clinical frontiers that characterize the forthcoming chapter in this domain. Full article

The human gut microbiome comprises a diverse community of bacteria whose interactions with the host range from beneficial mutualism to opportunistic pathogenicity. These interactions are shaped by genomic plasticity and ecological pressures that influence whether microbes support host health, remain conditionally harmless, or contribute to disease. Understanding the mechanisms underlying these shifts is essential for clarifying the balance between cooperation and pathogenicity within the gut ecosystem. This review explores the genomic and evolutionary mechanisms that shape microbial adaptation across the mutualism–pathogenicity spectrum in the human gut. Key processes, including horizontal gene transfer (HGT), host-mediated selection, and niche specialization, enable microbes to acquire, regulate, or retain traits that influence colonization, metabolic function, and virulence. These adaptive mechanisms allow gut bacteria to respond dynamically to ecological pressures such as inflammation, antibiotic exposure, and dietary change, resulting in context-dependent microbial behaviors. The review also considers how concepts from insect endosymbiosis may provide insight into gut microbial adaptation. While both systems exhibit host specialization, major differences in transmission mode, ecological flexibility, and genome evolution limit direct comparisons. Rather than following a fixed progression toward parasitism, gut microbes exhibit flexible adaptive strategies shaped by host and environmental conditions. By integrating ecological and evolutionary perspectives, this review presents a balanced framework for understanding how genomic adaptation influences microbial behavior in the gut. This perspective improves our understanding of dysbiosis and microbial pathogenesis and may support the development of microbiome-informed therapeutic strategies for maintaining host health. Full article

Witches’ broom disease (WBD), caused by the fungus Moniliophthora perniciosa, poses a major threat to cocoa production and little is yet known about how the fungus adapts at the molecular level, particularly in the apoplastic environment during early infection. Here, we investigated how apoplastic washing fluid (AWF) from two cocoa genotypes with contrasting resistance to WBD modulates the mycelial protein profile of two M. perniciosa isolates: (i) Mp553—low infection level; and (ii) Mp565—high infection level. A total of 1272 proteins were identified. Mp565, showed increased accumulation of proteins associated with oxidative stress response, energy metabolism, and virulence when exposed to AWF from the resistant variety TSH1188. Key proteins such as phosphoglycerate kinase, enolase, and heat shock were significantly modulated. Interestingly, AWF from the resistant variety promoted the suppression of metabolic proteins, suggesting an effective defense response in the resistant genotype. Furthermore, interaction network analysis revealed the central role of the MPER_11800 protein, a potential regulator of fungal adaptation. The findings underscore the importance of the T. cacao apoplast in both plant defense and fungal adaptation. The study also reveals key molecular targets, such as MPER_11800, for potential strategies to control WBD. These insights enhance our understanding of M. perniciosa pathogenicity and offer valuable directions for developing novel interventions to mitigate the impact of this devastating disease. Full article

Bombyx batryticatus is a traditional Chinese medicinal material derived from Bombyx mori infected by Beauveria bassiana; however, its formation mechanism remains poorly understood. This study compared infection processes in silkworms by two B. bassiana strains with markedly different virulence (highly virulent ZY027 and ARSEF2860). Integrated transcriptomic and proteomic analyses were employed to uncover, for the first time, the molecular basis of B. batryticatus formation at the systems biology level. The results demonstrated significant weight variations in B. batryticatus derived from different fungal strains. ZY027-induced stiff silkworms exhibited higher wet and dry weights than those infected by ARSEF2860. Large-scale gene reprogramming occurred in silkworm hemolymph post-infection, involving marked activation of Toll/Imd immune signaling pathways, ribosome biogenesis, and endoplasmic reticulum stress responses. A notable “uncoupling” between transcriptomic and proteomic profiles was identified, highlighting the critical role of post-translational regulation in host responses. The two strains triggered distinct metabolic reprogramming patterns: ZY027 notably suppressed oxidative phosphorylation and activated detoxification mechanisms, whereas ARSEF2860 presented characteristics of “immune–metabolic optimization.” These findings suggest that B. batryticatus formation involves complex fungus–silkworm molecular interactions in hemolymph, and that fungal strain characteristics are associated with significant differences in host molecular responses and product biomass. The study provides a theoretical foundation and innovative guidance for selecting strains with high B. batryticatus production potential and developing novel entomopathogenic fungal resources. Full article

Bacterial two-component systems (TCSs) mediate environmental sensing and adaptive responses through signal transduction between histidine kinases (HKs) and response regulators (RRs), thereby regulating biochemical processes essential for survival and, in pathogenic species, infection. How signaling specificity and insulation are maintained in organisms encoding multiple paralogous two-component systems remains an open question. Here, we investigate specificity in the Actinobacillus pleuropneumoniae TCS signaling network using an integrated computational framework that combines coevolutionary analysis, structural modeling, molecular dynamics simulations, and free-energy calculations. We show that cognate HK-RR recognition is established locally through clusters of coevolving interface residues, termed the orthologue interface specificity core (OISC), which mediate symmetric molecular recognition at individual interaction interfaces. However, interface-level recognition alone is insufficient to explain signaling fidelity across the network. Instead, system-wide specificity and pathway insulation emerge in this network from asymmetric energetic discrimination among cognate and non-cognate interactions across the ensemble of paralogous interfaces. Graded free-energy profiles reveal that broadly compatible interfaces can coexist with robust signaling insulation, reconciling interface promiscuity with stable network organization. Together, these findings support a two-tiered model for the TCS network analyzed here, in which symmetric interface constraints enable cognate recognition, while asymmetric network-level energetics govern signaling specificity. This framework may extend to other paralogous TCS networks. Full article

Background: Klebsiella pneumoniae is a globally relevant pathogen whose growing association between hypervirulence and antimicrobial resistance represents a major public health challenge. Methods: A systematic review was performed following the PRISMA 2020 guidelines. Studies published between 2005 and 2025 were searched in Google Scholar, Scopus, PubMed and Science Direct that reported the molecular detection of virulence genes in clinical isolates. Results: A total of 676 studies were included, in which 475 virulence genes were reported. A progressive increase in their detection was observed, Hypervirulent strains were associated with a higher proportion of genes associated with capsule and hypermucoviscosity, while classical strains were associated with a higher representation of adhesion and biofilm genes. Conclusions: The virulence of K. pneumoniae is organized into functional modules dominated by iron acquisition and capsular regulation. These findings support the prioritization of key determinants for molecular surveillance and the study of the global distribution and temporal trends of this pathogen. Full article

Staphylococcus aureus (S. aureus) bovine mastitis is a significant public health issue. Despite enormous efforts, important gaps remain regarding host–microenvironmental factors. How intramammary reduced oxygen modulates S. aureus transcription in bovine mammary epithelial cells (MECs) remains unclear. We examined oxygen-associated transcriptional changes in a bovine-mammary adapted S. aureus clone following internalization into MECs and identified functional category enrichments under Normal-O₂ and Reduced-O₂ exposures. Bovine MAC-T monolayers were infected with a dominant bovine mastitis isolate under Normal-O₂ or Reduced-O₂ conditions. Triplicate infection experiments were performed for each oxygen condition. Each condition included matched non-reacted bacterial controls maintained under the same gas condition but without MAC-T exposure serving as the reference condition for expression calling. RNA was extracted and profiled using a high-throughput qRT-PCR platform covering genome-wide loci. Expression calls were mapped to curated BioQT roles and interpreted descriptively. Results indicated 211 loci were upregulated and 99 were downregulated under Normal-O₂ conditions, versus 53 upregulated and 35 downregulated under Reduced-O₂ conditions, relative to their non-reacted controls. Under Normal-O₂ conditions, regulated loci covered multiple functional roles, including cellular processes, transport/binding proteins, regulatory functions, and energy metabolism with downregulated loci enriched in transport/binding and cell-envelope categories. Under Reduced-O₂ conditions, upregulated loci were abundant in cellular process annotations dominated by pathogenesis/toxin-related functions, whereas downregulated loci were enriched in nucleotide biosynthetic and DNA/cell division categories. Thus, this reveals oxygen-associated shifts in the transcriptional response of intramammary S. aureus in MAC-T cells. Normal-O₂ conditions were associated with broader category representation, whereas Reduced-O₂ conditions yielded a narrower distribution enriched for selected toxin/pathogenesis- and iron/cation-associated annotations. These oxygen-linked transcriptional-shifts highlight candidate pathways for the intramammary adaptation of S. aureus, potential diagnostic markers, anti-virulence strategies, and targeted therapeutics. Full article

Autophagy, also referred to as the “self-eating machinery”, is a crucial process where organisms maintain intracellular homeostasis through recycling or degrading non-essential and damaged cellular components. It is important in numerous biological functions such as cellular differentiation, aging, nutrient sensing, stress response, tissue homeostasis, immunity, and programmed cell death. Autophagy induction occurs with the formation of a double-layered membrane structure called “autophagosome”. The autophagosome wraps damaged organelles or proteins and transports them to the vacuole or lysosome for degradation. Autophagy is beneficial to organisms, and it should be optimally regulated because elevated or decreased levels are detrimental for survival. To date, more than 40 autophagy-related genes (ATGs) have been identified in the budding yeast Saccharomyces cerevisiae, with most having homologs in fungi and higher eukaryotes. Majority of the ATGs in industrial and pathogenic fungal species have been characterized and known to play vital roles in growth, development, and virulence. In this review we provide a comprehensive overview of ATGs in various fungal species and highlight how autophagy is regulated and controls various functions in plant, human, and industrial fungal species. Full article

The emergence of vancomycin-intermediate Staphylococcus aureus (VISA) threatens the efficacy of this last-line antibiotic. The GraSR two-component system is frequently mutated in VISA strains. Here, we demonstrate that the GraS(T136I) point mutation, identified in the clinical VISA isolate XN108, is a key determinant of reduced vancomycin susceptibility. Introducing this mutation into the susceptible strain Newman increased the vancomycin MIC from 1.5 to 4 mg/L, while its reversion in XN108 decreased the MIC from 12 to 8 mg/L. The mutation conferred common phenotypes, including thickened cell wall, decreased autolysis, and reduced cell surface negative charge via upregulation of the dltABCD operon and mprF. Notably, the GraS(T136I) mutation also upregulated virulence genes (efb, hlb, sbi, hld) and enhanced hemolytic activity. Interestingly, despite this hypervirulent profile, the mutant showed impaired long-term survival within macrophages. Our study reveals that a single GraSR mutation can co-regulate vancomycin resistance and virulence, offering new insights into the adaptation of S. aureus to antibiotic pressure. Full article